Note: Niraparib is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]). Do not initiate niraparib until hematologic toxicity due to previous chemotherapy has resolved to ≤ grade 1.
Ovarian, fallopian tube, or primary peritoneal cancer, advanced, first-line maintenance therapy:
Note: Begin niraparib no later than 12 weeks following the most recent platinum-containing regimen; continue until disease progression or unacceptable toxicity (González-Martin 2019).
Patients <77 kg or with a platelet count <150,000/mm3: Oral: 200 mg once daily (González-Martin 2019).
Patients ≥77 kg and with a platelet count ≥150,000/mm3: Oral: 300 mg once daily (González-Martin 2019).
Guideline recommendations: Newly diagnosed stage III to IV epithelial ovarian cancer (high-grade serous or endometrioid) in complete or partial response to first-line platinum-based chemotherapy: Oral: 200 to 300 mg once daily for 3 years; consider longer durations in individuals with partial response to platinum-based chemotherapy and demonstrating clinical improvement with niraparib (ASCO [Tew 2020]; Tew 2022).
Ovarian, fallopian tube, or primary peritoneal cancer, recurrent, maintenance treatment:
Oral: 300 mg once daily, continue until disease progression or unacceptable toxicity (Mirza 2016) or 200 to 300 mg once daily until disease progression or unacceptable toxicity (ASCO [Tew 2020]). Begin niraparib no later than 8 weeks following the most recent platinum-containing regimen.
Reduced initial dosing strategy (off label): Oral: Patients weighing <77 kg and/or with baseline platelets <150,000/mm3: Initial: 200 mg once daily (Berek 2018; Moore 2018). After 2 to 3 months, in the absence of hematologic toxicity, may consider escalation to usual dose of 300 mg once daily (Moore 2018).
Missed/vomited doses: If a dose is missed, administer the next dose at the regularly scheduled time. If a dose is missed or vomited, do not administer an additional dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney function estimated using the Cockcroft-Gault formula.
CrCl 30 to <90 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End stage renal disease: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic function estimated using the National Cancer Institute Organ Dysfunction Working Group Criteria.
Mild impairment (total bilirubin <1.5 × ULN and any AST or bilirubin ≤ ULN and AST > ULN): No dosage adjustment necessary.
Moderate impairment (total bilirubin ≥1.5 to 3 × ULN and any AST): Reduce initial dose to 200 mg once daily; monitor for hematologic toxicity and reduce dose further if needed.
Severe impairment (total bilirubin >3 × ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
Adverse reactions may be managed with treatment interruption, dose reduction, and/or discontinuation.
|
Starting (initial) dose level |
200 mg once daily |
300 mg once daily |
|---|---|---|
|
aIf further dose reduction below 100 mg once daily is necessary, discontinue niraparib. | ||
|
First dose reduction |
100 mg once dailya |
200 mg once daily |
|
Second dose reduction |
Discontinue niraparib |
100 mg once dailya |
Hematologic toxicity:
Platelets <100,000/mm3:
First occurrence: Withhold niraparib for a maximum of 28 days and monitor blood counts weekly. When platelets are ≥100,000/mm3, resume niraparib at the same or at a reduced dose. If platelet count was <75,000/mm3, resume at a reduced dose.
Second occurrence: Withhold niraparib for a maximum of 28 days and monitor blood counts weekly. When platelets are ≥100,000/mm3, resume niraparib at a reduced dose. Discontinue if platelet count has not returned to acceptable levels within 28 days of interrupting dose, or if dose has already been reduced to 100 mg once daily.
Neutrophils <1,000/mm3 or hemoglobin <8 g/dL: Withhold niraparib for a maximum of 28 days and monitor blood counts weekly. When neutrophils are ≥1,500/mm3 or hemoglobin is ≥9 g/dL, resume niraparib at a reduced dose. Discontinue if neutrophils and/or hemoglobin have not returned to acceptable levels within 28 days of interrupting dose, or if dose has already been reduced to 100 mg once daily.
Neutropenia (grade 4 lasting ≥5 to 7 days or associated with fever): Withhold niraparib until recovery of infection and granulocyte count, then reinitiate with the niraparib dose reduced. WBC growth factor support may be used while niraparib is withheld for neutropenia; however, growth factors are not indicated during daily niraparib dosing (ASCO (Tew 2020]).
Hematologic toxicity requiring transfusion: Withhold niraparib. Consider platelet transfusion for platelets ≤10,000/mm3. If other risk factors (eg, concurrent anticoagulation or antiplatelet therapy), consider interrupting the anticoagulant/antiplatelet and/or transfusing to a higher platelet count. Resume niraparib at a reduced dose.
Persistent hematologic toxicity (≥28 days): If hematologic toxicities do not resolve within 28 days following interruption, discontinue niraparib and obtain consult with hematology for further assessment, including bone marrow and cytogenetic analysis.
Secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): Discontinue niraparib with confirmed diagnosis of MDS or AML.
Nonhematologic toxicity:
Grade 3 or higher adverse reaction that persists despite medical management: Withhold niraparib for a maximum of 28 days or until resolution; resume with the dose reduced.
Grade 3 or higher treatment-related adverse reaction lasting >28 days at a dose of 100 mg once daily: Discontinue niraparib.
GI toxicity: Persistent nausea requiring daily antiemetics, resulting in performance status reduction and/or resulting in >5% weight loss: Consider niraparib dose reduction (ASCO [Tew 2020]).
Hypertension: Manage with antihypertensives and niraparib dose adjustment if necessary.
Posterior reversible encephalopathy syndrome: Promptly discontinue niraparib and manage appropriately if posterior reversible encephalopathy syndrome (PRES) is suspected; the safety of reinitiating niraparib treatment in patients previously experiencing PRES is not known.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as tosylate:
Zejula: 100 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #5 (tartrazine)]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as tosylate:
Zejula: 100 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #5 (tartrazine)]
Oral: Administer at approximately the same time each day, either with or without food. Swallow capsules whole; do not chew, crush, or split. Niraparib is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]). Consider administering at bedtime to diminish the potential for nausea and vomiting.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Niraparib may cause carcinogenicity, teratogenicity, reproductive toxicity, and genotoxicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Ovarian, fallopian tube, or primary peritoneal cancer:
First-line maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults who are in a complete or partial response to first-line platinum-based chemotherapy.
Maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults who are in a complete or partial response to platinum-based chemotherapy.
Niraparib may be confused with enasidenib, neratinib, nilotinib, nintedanib, olaparib, rucaparib, talazoparib.
Zejula may be confused with Jevtana, Xgeva, Xofigo, Xtandi, Zepzelca, Zometa, Zydelig, Zytiga.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Hypertension (18% to 20%)
Dermatologic: Skin rash (21%)
Endocrine: Decreased serum magnesium (36%), increased serum glucose (66%)
Gastrointestinal: Constipation (40%), decreased appetite (19% to 25%), dyspepsia (18%), nausea (57% to 74%; grades 3/4: 1% to 3%), stomatitis (20%; grades 3/4: <1%), vomiting (22% to 34%; grades 3/4: 1% to 2%)
Genitourinary: Urinary tract infection (13%)
Hematologic & oncologic: Anemia (50% to 64%; grades 3/4: 25% to 31%), leukopenia (17% to 28%; grades 3/4: 5%), lymphocytopenia (51%; grades 3/4: 7%), neutropenia (30% to 42%; grades 3/4: 20% to 21%), thrombocytopenia (61% to 66%; grades 3/4: 29% to 39%)
Hepatic: Increased serum alanine aminotransferase (≤29%), increased serum alkaline phosphatase (46%), increased serum aspartate aminotransferase (≤36%)
Nervous system: Anxiety (11%), asthenia (≤57%), dizziness (18% to 19%), fatigue (≤57%), headache (26%), insomnia (25% to 27%)
Neuromuscular & skeletal: Back pain (18%), musculoskeletal pain (39%)
Renal: Acute kidney injury (12%), increased serum creatinine (40%)
Respiratory: Cough (16% to 18%), dyspnea (20% to 22%), nasopharyngitis (23%)
1% to 10%:
Cardiovascular: Palpitations (10%), peripheral edema, tachycardia
Endocrine & metabolic: Hypokalemia, weight loss
Gastrointestinal: Dysgeusia (10%), xerostomia (10%)
Hepatic: Increased gamma-glutamyl transferase
Nervous system: Depression
Ophthalmic: Conjunctivitis
Respiratory: Bronchitis, epistaxis
<1%:
Hematologic & oncologic: Acute myelocytic leukemia, myelodysplastic syndrome
Nervous system: Reversible posterior leukoencephalopathy syndrome
Frequency not defined: Gastrointestinal: Intestinal obstruction (small intestinal obstruction)
Postmarketing:
Cardiovascular: Hypertensive crisis
Dermatologic: Skin photosensitivity
Hematologic & oncologic: Pancytopenia
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Nervous system: Cognitive dysfunction (including lack of concentration, memory impairment), confusion, disorientation, hallucination
Respiratory: Pneumonia
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to niraparib or any component of the formulation; breastfeeding.
Concerns related to adverse effects:
• Bone marrow suppression: Thrombocytopenia, anemia, neutropenia, and/or pancytopenia have been reported with niraparib, including grade 3 or higher thrombocytopenia, neutropenia, and anemia.
• Cardiovascular effects: Hypertension and hypertensive crisis have been reported, including grade 3 and 4 hypertension (hypertension required discontinuation in rare cases). The median time from the first niraparib dose to hypertension onset was 15 to 77 days (range: 1 to 531 days). The median duration of hypertension was 7 to 15 days (range: 1 to 118 days). Patients with cardiac disorders (especially coronary insufficiency, arrhythmias, and hypertension) should be monitored closely.
• Posterior reversible encephalopathy syndrome: Posterior reversible encephalopathy syndrome (PRES) has occurred rarely with niraparib. Signs/symptoms of PRES include seizure, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension.
• Secondary malignancy: Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) have been reported (rare) with niraparib monotherapy, including fatal cases. The duration of niraparib therapy prior to the development of treatment-related MDS/AML varied from <1 month to ~5 years. All patients had received prior chemotherapy with platinum-based regimens and/or other DNA-damaging agents, including radiotherapy.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
• Yellow dye: Niraparib contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in some patients. While the incidence of tartrazine sensitivity in the overall population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
Substrate of BCRP/ABCG2, P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Apalutamide: May enhance the adverse/toxic effect of Niraparib. Apalutamide may decrease the serum concentration of Niraparib. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased niraparib concentrations and efficacy, as well as for increased niraparib toxicities. Risk D: Consider therapy modification
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Verify pregnancy status prior to treatment initiation. Patients who could become pregnant should use effective contraception during therapy and for at least 6 months after the last niraparib dose.
Animal reproduction studies have not been conducted, however based on the mechanism of action, in utero exposure to niraparib may cause fetal harm.
It is not known if niraparib is present in breast milk.
Due to the potential for serious adverse events in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 month after the last niraparib dose.
CBC with differential (weekly for the first month, then monthly for 11 months, then periodically). Evaluate pregnancy status prior to treatment (in patients who could become pregnant). Monitor BP and heart rate at least weekly for the first 2 months, then monthly for the first year and periodically thereafter (monitor patients with cardiac disorders, especially coronary insufficiency, arrhythmias, and hypertension more closely). Monitor for signs/symptoms of posterior reversible encephalopathy syndrome (brain imaging [preferably MRI] is required for diagnosis) and secondary malignancy. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow up.
Niraparib is a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, which is highly selective for PARP-1 and PARP-2. PARP-1 and PARP-2 are involved in detecting DNA damage and promote repair (Mirza 2016). Inhibiting PARP enzymatic activity results in DNA damage, apoptosis and cell death. Niraparib induces cytotoxicity in tumor cell lines with and without BRCA1/2 deficiencies.
Distribution: Vd/F: 1,074 L
Protein binding: 83%
Metabolism: Metabolized by carboxylesterases to an inactive metabolite, which subsequently undergoes glucuronidation.
Bioavailability: ~73%
Half-life elimination: 36 hours
Time to peak: Within 3 hours
Excretion: Urine (~48% [at 21 days]; 11% [pooled samples collected over 6 days] as unchanged drug); Feces (~39% [at 21 days]; 19% [pooled samples collected over 6 days] as unchanged drug)
Following a single 300 mg dose in patients with moderate hepatic impairment (total bilirubin ≥1.5 to 3 × ULN and any AST), the niraparib AUCinf was 1.56 times higher (compared with patients with normal hepatic function).
Capsules (Zejula Oral)
100 mg (per each): $326.21
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